5-6 - LICENSE REVOCATION OR SUSPENSION

5-6-1 - Purpose

This section contains procedures for revoking and suspending biologic licenses issued under the Public Health Service Act. These procedures are applicable to actions recommended by the field or by CBER.

"Revocation" is the cancellation of a license and the withdrawal of the authorization to introduce or deliver for introduction into interstate commerce, biological products, at either the request of the manufacturer or when grounds exist for the Agency to initiate such an action.

"Suspension" is a summary action taken by the Agency and may be an initial or intermediate step in the revocation process. Suspension provides for the immediate withdrawal of the authorization to introduce or deliver for introduction, biological products into interstate commerce when the Commissioner has reasonable grounds to believe that any of the grounds for revocation exist and that by reason thereof there is a danger to health.

5-6-2 - General

Licenses issued for the manufacture of specific biologic products under the provisions of Section 351(a) of the PHS Act, may be: 1) revoked upon request of the licensee or by initiative of the Commissioner when sufficient grounds exist; or 2) suspended if one or more of the grounds for revocation exists and presents a danger to health (see 21 CFR 601.5 and 601.6).

CBER's Office of Compliance and Biologics Quality (OCBQ), Division of Case Management (DCM) reviews recommendations for license revocation and suspension proposed by the field offices or the appropriate unit within CBER. If DCM concurs with the recommendation, it is forwarded to the Office of Chief Counsel (OCC) for review. If OCC concurs, the recommendation and action letter are sent to the Director, CBER for concurrence and signature. Pursuant to SMG 1410.203, the Commissioner has delegated the authority to issue notices of revocation and suspension to the Director and Deputy Director, CBER.

OCBQ ensures that recommendations for license revocation or suspension are supported with evidence of violations of the applicable statutes and regulations. License suspensions and revocations are significant enforcement actions with possible far-reaching consequences. As such, it is important to consider the impact that the action may have on product supply as part of the Agency's review of a proposed license suspension or revocation action.

When the license relates to multiple locations, revocation may be limited to one or more of the locations, if inspectional findings support that approach.

In the absence of willful noncompliance or a history of violations of a significant nature, the district or CBER inspection review unit considers issuing a Warning Letter or conducting a meeting with the firm, rather than recommending revocation as a first choice remedy.

5-6-3 - General Considerations For Revocation

The Agency may consider revocation of a biologic license when any of the conditions specified in 21 CFR 601.5 exist. In establishing that the grounds for revocation in 21 CFR 601.5 are met, the recommending unit considers the two courses of action provided in the regulations: 1) notice of intent to revoke with the possibility of demonstrating or achieving compliance, or 2) in cases involving willfulness, notice of FDA's intention to move directly to revocation without providing an opportunity to demonstrate or achieve compliance.

Notice of Intent to Revoke

Inspectional findings must demonstrate a current history of repeated or continuous significant deviations that represent a breakdown of process controls, rather than isolated incidents. Ordinarily, a demonstration of prior warning to the firm is via Warning Letter and/or a meeting or other contact with the firm before consideration of license revocation. If a past Warning Letter issued and one or more non-violative inspection(s) follows it, a recommendation for license revocation based on current significant deficiencies must document whether the deficiencies are of a continuing nature and how the current inspection relates to any previous inspection which resulted in the Warning Letter or other communication with the firm that provided the firm notice of such deficiencies. Issuance of a Warning letter in the past may not preclude issuance of an additional Warning Letter, especially if the nature and cause of the violation have changed. For example, a firm issued a Warning Letter three years ago for viral marker testing violations may warrant issuance of another Warning Letter or other action, rather than proceeding to license revocation, if the current inspection shows violations in different areas of the operation or manufacturing practices, e.g., computer validation.

In addition, FDA may proceed to revocation upon suspension of a license, as provided by 21 CFR 601.6(b).

Upon issuance of a "Notice of Intent to Revoke" letter (except in cases involving willfulness), we provide the licensee an opportunity to demonstrate or achieve compliance before instituting proceedings for revocation of the license.

Willful conduct is established by showing that an individual: 1) knowingly committed a prohibited act, such as records falsification or concealment; or 2) acted with careless disregard of the regulatory requirements, as exemplified by repeatedly failing to correct violations. In cases involving willfulness, FDA ordinarily does not provide the licensee with the opportunity to demonstrate or achieve compliance, in accordance with 21 CFR 601.5(b). In all cases, FDA notifies the licensee of the opportunity to request a hearing pursuant to 21 CFR 12.21(b).

5-6-4 - Issues Not Supporting License Revocation

CBER ordinarily will not support license revocation when the following issues are the basis for the recommendation to revoke:

Biological Product Deviation Reports

Biological product deviation reports, in and of themselves, ordinarily may not form the basis for a license revocation unless the firm failed to recognize the error, failed to investigate and properly document the investigation, and/or failed to implement corrective action to prevent its recurrence, or failed to notify FDA if so required under 21 CFR 600.14. In addition, in order to meet the grounds for license revocation, the deviation must be of such a nature or extent as to represent a firm's failure to establish or maintain control over one or more of the systems employed for the manufacture of biological products.

Isolated Incidents

Isolated occurrences do not ordinarily establish grounds for license revocation, unless there is documentation to demonstrate that the occurrences represent a pattern of violative activity.

Past Violations

Violations that occurred prior to the current FDA inspection (and for which implementation of appropriate corrective action prevents reoccurrence) ordinarily do not form the basis for license revocation. However, FDA must document previous violations even with correction, or no repeats, because they may demonstrate a pattern or history of non-compliance. If violations persist, such a pattern is pertinent to a future decision to proceed to revocation.

5-6-5 - Revocation Procedures

If the inspection review unit is considering revocation as an enforcement option, contact CBER, DCM, during the inspection or soon after issuance of the FDA 483. Discussions with CBER prior to submission of a recommendation will facilitate the processing of the recommendation.

If the inspection review unit believes license revocation is appropriate, that office submits a recommendation to DCM for revocation with supporting documentation. Include the district director's concurrence on recommendations for revocation. In addition to forwarding documentation of the violations, the recommending unit submits a detailed summary of the firm's inspectional and compliance history over the past five years. The recommending unit also assesses the impact of license revocation on the supply of the biological products involved. The initial CBER contact is DCM, HFM-610, (301) 827-6201, FAX: (301) 594-0940.

CBER assigns a consumer safety officer from HFM-610 to each revocation recommendation. If using express delivery, send to:

CBER personnel review the information received and determine whether the inspectional findings support revocation of the firm's license.

If CBER does not concur with the revocation recommendation, it communicates its decision to the recommending unit. CBER sends a memorandum confirming the reasons for the disapproval and provides other enforcement options, if appropriate.

If CBER concurs with the district’s recommendation, it prepares an Action Memorandum with supporting documentation to the Director, CBER, and a letter notifying the licensee of the Agency's intention to initiate proceedings to revoke the license. This package is forwarded to the Office of Chief Counsel (OCC) for review (see RPM Chapter 4, Exhibit 4-1). If OCC concurs, the recommendation and action letter are sent to the Director, CBER for concurrence and signature. Recommendations that CBER has initiated are also routed to the Director of CBER for clearance. Prior to doing so, however, the CBER initiating office contacts the appropriate district office to advise the district of the action proposed by CBER.

After the Director signs the letter, the Director, DCM verbally advises the most responsible person at the firm of the Agency's intention to revoke the license. DCM then transmits a copy of the letter to the firm via facsimile and mails the original letter as Certified/Return Receipt Requested.

CBER’s OCBQ advises the district office and/or recommending unit within CBER of the action concurrently. In addition, they transmit copies of the Action Memorandum and the revocation letter to the recommending unit via facsimile or electronic mail.

Both CBER and the recommending unit review the establishment's response to the letter of revocation expeditiously. The recommending unit provides CBER with its conclusions and comments regarding the adequacy of the firm's response.

The Agency usually gives an establishment the opportunity to demonstrate or achieve compliance. If the establishment has not waived its opportunity for a hearing by voluntarily requesting revocation, CBER's OCBQ and the firm continue to correspond until all corrective actions appear satisfactory. CBER will distribute copies of all correspondence between CBER and the firm to the recommending unit for review. When the recommending unit and CBER's OCBQ agree that all corrective actions appear satisfactory, CBER will ask the district office to conduct a follow up inspection expeditiously.

The district will advise CBER of the approximate date of reinspection and notify CBER by telephone or electronically of its findings and recommendation. Afterwards, the district sends a written recommendation either to move toward revocation or to discontinue proceedings for license revocation.

In some instances, the firm may have made significant progress in demonstrating or achieving compliance, but after review of the FDA 483 and the firm's response(s), the district and/or CBER may view a limited follow-up inspection as necessary prior to making a final determination on the matter of revocation.

Following reinspection, if CBER and the district determine that the firm demonstrated or achieved compliance, CBER will notify the firm of this determination.

In cases involving willfulness, ordinarily the establishment has 10 days from the date of the revocation letter to waive the opportunity for hearing by requesting voluntary revocation in writing. If the establishment does not waive the opportunity for a hearing by surrendering the license within the ten-day time frame, DCM forwards a request to the Division of Regulations and Policy, HFM-17, to prepare the Federal Register Notice of Opportunity for Hearing.

FDA publishes the Notice of Opportunity for Hearing on a proposal to revoke a license in the Federal Register together with an explanation of the grounds for the proposed action. A person subject to the notice has 30 days after its issuance to request a hearing. There is no extension of the 30-day period. A request for hearing must set forth specific facts showing that there is a genuine and substantial issue of fact that justifies a hearing, and may not rely upon mere allegations or denials.

5-6-6 - General Considerations For Suspension

Pursuant to 21 CFR 601.6, the Commissioner may suspend a license if the Commissioner has reasonable grounds to believe that any of the grounds for revocation exist and that by reason thereof there is a danger to health. Investigators obtain documentary evidence to support revocation and danger to health, and CBER conducts an evaluation of the danger to health.

Once CBER determines that a danger to health exists, the recommending unit immediately contacts the appropriate state health authorities. In addition, the district considers legal actions such as injunction or seizure, particularly if a given state health department lacks regulatory authority over intrastate operations or if the license suspension does not result in immediate corrective action. The recommending unit provides CBER with any information obtained regarding the state health department authority and the likelihood it may take regulatory action based on FDA's findings.

If a blood establishment is involved, the recommending unit determines the approximate number of annual collections and the percentage of blood products distributed in interstate commerce. The recommending unit, together with CBER, examines supply issues and considers contacting the large national blood organizations to ensure that a license suspension will not adversely affect the public health.

As in the case of revocation, when there are multiple locations encompassed by one license, suspension may be limited to one or more of the locations, if inspectional findings warrant that approach.

5-6-7 - Suspension Procedures

If the inspecting unit believes a danger to health exists, it should contact CBER’s DCM, HFM-610, 301-827-6201 immediately, during the inspection, and provide specific, substantive information relating to the grounds for suspension. It must not wait until the conclusion of the inspection to make contact. At that time, DCM assigns a consumer safety officer from HFM-610 to the suspension recommendation who will work with the investigators in case development.

The inspecting unit should transmit a copy of the FDA 483 (draft or final copy) as quickly as possible to DCM by facsimile, electronic mail, or express delivery, along with any additional requested preliminary information and/or documentation. To avoid delay, do not send supporting documentation through the regular mail system if other means of transmission are available. If using overnight express delivery, send to:

DCM will consult, as necessary, with the appropriate scientific/medical staff to determine if a danger to health exists. If a danger to health exists, the inspecting office will be advised and should submit a recommendation in a brief memorandum that includes the basis of the recommendation. Transmit the recommendation by facsimile (301-594-0940) or by electronic mail. Recommendations for suspension are given a high priority and supervisors are to act promptly. Recommendations for suspension should have the concurrence of the district director. The district will make every effort to expedite the submission of a recommendation to CBER to suspend operations under license at an establishment whose practices present an imminent danger to health.

Frequently DCM may concur with a suspension recommendation after receiving the FDA 483 but before receiving the Establishment Inspection Report (EIR). In cases involving complex issues, DCM may need to review the completed EIR before reaching a decision. In either event, write the EIR promptly and forward by express mail service to DCM.

Depending upon the products involved, CBER may ask the recommending unit to obtain a complete inventory of the products on the firm's premises.

If DCM concurs with the suspension recommendation, it will prepare an Action Memorandum and a letter of suspension within three working days of receipt of the recommendation. Documents will be sent to OCC for review as soon as available (see RPM Chapter 4, Exhibit 4-1). Upon OCC concurrence, the Director, CBER, who notes the date and time of signature, signs the Action Memorandum and letter of suspension. The Director, OCBQ or DCM will immediately telephone the firm and advise it of the suspension of its biologics license. DCM will then send the letter to the firm by facsimile and certified mail.

CBER may concurrently advise the recommending unit of FDA's action. In some situations, CBER may arrange to transmit a copy of the suspension letter to the district for hand delivery to the firm.

If CBER does not concur with a suspension recommendation, it communicates its decision to the recommending unit. DCM will prepare a memorandum explaining the reasons for the disapproval. If CBER disagrees with the suspension recommendation based on the absence of a danger to health, and any of the conditions specified in 21 CFR 601.5(b) exist, DCM considers whether it is appropriate to revoke the license or send a Warning Letter and will discuss these options with the recommending unit.

DCM and the recommending unit concurrently review the reply to a letter of suspension and continue to correspond with the firm until both agree that all corrective actions appear satisfactory. At this point, DCM notifies the firm, ordinarily by telephone (later confirmed by letter), that limited operations may resume for the purpose of a reinspection to determine that the corrective actions implemented are effective. CBER requests that the district office conduct a follow up inspection expeditiously, generally within 30 days of resumption of limited operations.

The district office advises CBER of the approximate date of reinspection. As soon as possible upon its conclusion, the district notifies CBER by telephone of its findings and recommendation (CBER contact is DCM, HFM-610, 301-827-6201). The district follows-up by sending a written recommendation on the last day of the inspection or shortly thereafter. If issuing a FDA 483, the district forwards a copy of the firm's response, if any, to CBER. In addition, the district sends a written copy of the establishment inspection report to CBER as quickly as possible to support continued suspension, revocation or reinstatement.

In some instances the firm may have made significant progress in achieving compliance, but after review of the FDA 483 and the firm's response(s), the district and/or CBER may view a limited follow-up inspection as necessary prior to making a final determination as to whether to recommend reinstatement of the license.

If the follow-up inspection indicates inadequate corrective actions and continued deviations, the district obtains additional documentation and notifies CBER as soon as possible. CBER decides whether to allow the firm to continue in limited operations or to cease all operations. In addition, CBER considers the possibility of proceeding toward license revocation.

If the firm is achieving compliance, CBER prepares an Action Memorandum and letter of reinstatement for the signature of the Director, CBER. After the letter is signed, the Director OCBQ or DCM telephones the firm and advises it that the Agency has lifted the suspension of the firm's activities and they may now ship products collected or manufactured since the date they resumed limited operations. Also, DCM advises the district by telephone and sends a copy of the reinstatement letter, which, if appropriate, may contain instructions to the firm for filing a request to use products in inventory at the time of suspension.

On a case-by-case basis, CBER evaluates written requests for release of products in inventory at the time of suspension. Communicate in writing all decisions regarding the disposition of products to the firm (copy to the district). CBER may request that the district monitor the disposition of the inventory.

Send copies of all correspondence, verbal and written communications, and EIRs relating to suspensions of operations under license, to the attention of: